Listed in reverse date order:
|Suresh 1999||Subclinical hyperthyroidism and hyperkinetic behavior in children.|
|Erichsen 1998||Thyroid hormone resistance. Clinical, biochemical and genetic study of a family|
|Hauser 1998||Resistance to thyroid hormone: implications for neurodevelopmental research on the effects of thyroid hormone disruptors.|
|McDonald 1998||Hyperactivity and learning deficits in transgenic mice bearing a human mutant thyroid hormone beta1 receptor gene.|
|Hauser 1997||Thyroid hormones correlate with symptoms of hyperactivity but not inattention in attention deficit hyperactivity disorder.|
|Toren 1997||Thyroid function in attention deficit and hyperactivity disorder.|
|Valentine 1997||Thyroid function in a population of children with attention deficit hyperactivity disorder.|
|Weiss 1997||Phenotype differences of resistance to thyroid hormone in two unrelated families with an identical mutation in the thyroid hormone receptor beta gene (R320C).|
|Weiss 1997||Behavioral effects of liothyronine (L-T3) in children with attention deficit hyperactivity disorder in the presence and absence of resistance to thyroid hormone.|
|Kopp 1996||Syndrome of resistance to thyroid hormone: insights into thyroid hormone action.|
|Matochik 1996||Abnormalities in sustained attention and anterior cingulate metabolism in subjects with resistance to thyroid hormone.|
|Rovet 1996||Thyroid hormone and attention in school-age children with congenital hypothyroidism. |
|Seto 1996||Rapid molecular diagnosis of mutations associated with generalized thyroid hormone resistance by PCR-coupled automated direct sequencing of genomic DNA: detection of two novel mutations.|
|West 1996||Differences in thyroid function studies in acutely manic adolescents with and without attention deficit hyperactivity disorder (ADHD).|
|Brucker Davis 1995 ||Genetic and clinical features of 42 kindreds with resistance to thyroid hormone. The National Institutes of Health Prospective Study.|
|Leonard 1995||Magnetic resonance imaging of cerebral anomalies in subjects with resistance to thyroid hormone.|
|Hauser 1993||Attention deficit-hyperactivity disorder in people with generalized resistance to thyroid hormone.|
|Weiss 1993||Attention-deficit hyperactivity disorder and thyroid function.|
|Mixson 1992||Correlations of language abnormalities with localization of mutations in the beta-thyroid hormone receptor in 13 kindreds with generalized resistance to thyroid hormone: identification of four new mutations.|
Genetic and clinical features of 42 kindreds with resistance to thyroid
hormone. The National Institutes of Health Prospective Study.
Brucker-Davis F et al, Ann Intern Med 1995 Oct 15;123(8):572-83
with resistance to thyroid hormone from 42 kindreds and 114 unaffected relatives sharing the patients' environmental and
genetic backgrounds. ... In persons with resistance to thyroid hormone, we measured the increased incidence of goiter (65%),
attention-deficit hyperactivity disorder (60%), IQ less than 85 (38%), speech impediment (35%), and short stature (18%).
We also described new clinical features, such as frequent ear, nose, and throat infections (56%); low weight-for-height in
children (32%); hearing loss (21%); and cardiac abnormalities (18%). ..."
Thyroid hormone resistance. Clinical, biochemical and genetic study of
Erichsen KE, Berg JP, Torjesen PA, Haug E, Johannesen O,
Tidsskr Nor Laegeforen 1998 Feb 10;118(4):525-9
"We here present a family where three individuals in three generations had varying degrees of goiter, tachycardia, fatigue,
hyperactivity, and learning disability. Serum T3 and free T4 were elevated, whereas TSH was normal or slightly increased.
The clinical findings in combination with the hormone values led to several supplementary investigations and therapies being
carried out, but they had no beneficial influence on the patients' symptoms. ... This mutation has previously been shown to decrease receptor affinity for T3..."
Attention deficit-hyperactivity disorder in people with generalized
resistance to thyroid hormone.,
Hauser P, et al, New England Journal of Medicine 1993 Apr 8;328(14):997-1001
"...We systematically evaluated the presence and severity of attention deficit-hyperactivity disorder in 18
families with a history of generalized resistance to thyroid hormone. ... In our study sample, attention
deficit-hyperactivity disorder is strongly associated with generalized resistance to thyroid hormone. "
Resistance to thyroid hormone: implications for neurodevelopmental
research on the effects of thyroid hormone disruptors.,
Hauser P, McMillin JM, Bhatara VS,
Toxicol Ind Health 1998 Jan-Apr;14(1-2):85-101
". . .There is increasing evidence that exposure to certain
synthetic compounds, including dioxins and polychlorinated biphenyls (PCBs), during the perinatal period can also impair
learning, memory, and attentional processes in offspring. Animal and human
studies suggest that exposure to these environmental toxicants impair normal thyroid function.
Although the precise mechanisms of action of the adverse effects these toxicants have on
neurodevelopment have not yet been elucidated, it is possible that they are partially or
predominantly mediated by alterations in hormone binding to the thyroid hormone receptor. . .
Thyroid hormones correlate with symptoms of hyperactivity but not
inattention in attention deficit hyperactivity disorder.,
Hauser P, Soler R, Brucker-Davis F, Weintraub BD,
Psychoneuroendocrinology 1997 Feb;22(2):107-14
"... In this study, the relationship between thyroid hormones and symptoms of hyperactivity was
examined in subjects with resistance to thyroid hormone (RTH) and their unaffected family members. ... in the RTH [resistance to thyroid hormone] group, both
TT3 and TT4 concentrations were significantly and positively correlated with total symptoms of ADHD ... as
well as symptoms of inattention ... and symptoms of hyperactivity ... The data support the hypothesis that thyroid
hormones may provide a physiological basis for the dichotomy between symptoms of inattention and symptoms of
Syndrome of resistance to thyroid hormone: insights into thyroid
Kopp P, Kitajima K, Jameson JL,
Proc Soc Exp Biol Med 1996 Jan;211(1):49-61
"... Resistance to thyroid
hormone (RTH) is a rare disorder caused by mutations in the TR beta gene. Biochemically, the syndrome is defined by
elevated circulating levels of free thyroid hormones due to reduced target tissue responsiveness and normal, or elevated,
levels of thyroid-stimulating hormone (TSH). ... pituitary resistance results in hypersecretion of TSH, which
compensates, at least in part, for hormone resistance in peripheral tissues. Despite this compensation, clinical effects of
RTH can include short stature, delayed bone maturation, hyperactivity, learning disabilities, and hearing defects, ...".
Magnetic resonance imaging of cerebral anomalies in subjects with
resistance to thyroid hormone.
Leonard CM, Martinez P, Weintraub BD, Hauser P,
Am J Med Genet 1995 Jun 19;60(3):238-43
"... Individuals with RTH [resistance to thyroid hormone] have an increased incidence of attention deficit
hyperactivity disorder (ADHD). The purpose of this study was to search for developmental brain malformations
associated with RTH. ...Abnormal thyroid hormone action in the male fetus early during brain
development may be associated with grossly observable cerebral anomalies of the left hemisphere..."
Abnormalities in sustained attention and anterior cingulate metabolism
in subjects with resistance to thyroid hormone.
Matochik JA, Zametkin AJ, Cohen RM, Hauser P, Weintraub BD,
Brain Res 1996 Jun 3;723(1-2):23-8
"Attention deficit disorders are a frequent manifestation of resistance to thyroid hormone (RTH), a disorder caused by
mutations in the hormone-binding domain of the human thyroid hormone receptor beta gene. Positron emission
tomography was used to measure cerebral glucose metabolism in regions known to be biological determinants of sustained
attention ... Compared to the control group, performance ... was severely impaired in the RTH subjects, while metabolism was higher both in the right
parietal cortex and the anterior cingulate gyrus. ..."
Hyperactivity and learning deficits in transgenic mice bearing a human
mutant thyroid hormone beta1 receptor gene.
McDonald MP, Wong R, Goldstein G, Weintraub B, Cheng SY, Crawley JN,
Learn Mem 1998 Sep-Oct;5(4-5):289-301
"... The syndrome is characterized by reduced tissue responsiveness to thyroid
hormone and elevated serum levels of thyroid hormones. A common behavioral phenotype
associated with RTH [Resistance to Thyroid Hormone] is attention deficit hyperactivity disorder (ADHD).
. . . Male transgenic mice showed elevated locomotor
activity in an open field compared to male wild-type littermate controls. Both male and female
transgenic mice exhibited impaired learning of an autoshaping task, compared to wild-type
controls. . . . These results indicate that transgenic mice
bearing a mutant human TRbeta gene demonstrate several behavioral characteristics of ADHD
. . ."
Correlations of language abnormalities with localization of mutations in
the beta-thyroid hormone receptor in 13 kindreds with generalized
resistance to thyroid hormone: identification of four new mutations.
Mixson AJ, Parrilla R, Ransom SC, Wiggs EA, McClaskey JH, Hauser P, Weintraub BD,
J Clin Endocrinol Metab 1992 Oct;75(4):1039-45
"...Kindreds with mutations in exon 9 compared with those in exon 10 have
significantly more problems in language development, as manifested by articulation problems and/or wide discrepancies in
verbal and performance IQs. ..."
Thyroid hormone and attention in school-age children with congenital
Rovet J, Alvarez M,
J Child Psychol Psychiatry 1996 Jul;37(5):579-85
The relationship between attention and thyroid hormone was examined using a retrospective
database of 85 7-year-old children with congenital hypothyroidism who received psychological
evaluations and thyroid function tests on the same day. . . Children with high levels of both hormones were found to be significantly more
distractable on an index of cognitive attention but were reportedly less hyperactive. Level of
thyroxine accounted for over 10% of the variance in attention."
Rapid molecular diagnosis of mutations associated with generalized thyroid hormone resistance by PCR-coupled automated direct sequencing of genomic DNA: detection of two novel mutations.
Seto D, Weintraub BD,
Hum Mutat 1996;8(3):247-57
Generalized thyroid hormone resistance (GTHR) is a syndrome characterized by tissue
nonresponsiveness to thyroid hormones and by variable clinical phenotype manifestations. This
syndrome has also been implicated as a predisposing factor in some cases of attention
deficit-hyperactivity disorder (ADHD). GTHR results from single mutations in the gene encoding
the thyroid hormone receptor. . . . The rapid molecular diagnostic protocol, from whole blood
to DNA sequence data, takes approximately 15 hr, allowing for rapid, efficient, and unambiguous
direct detection of the mutant alleles."
Subclinical hyperthyroidism and hyperkinetic behavior in children.
Suresh PA, Sebastian S, George A, Radhakrishnan K,
Pediatr Neurol 1999 Mar;20(3):192-4
The authors report three children who exhibited developmental learning disabilities (DLDs)
associated with behavioral disturbances, such as attention deficit, hyperactivity, and autistic
features. The thyroid function tests performed as a part of routine endocrinologic evaluation of
children with DLDs revealed a hormonal profile consistent with hyperthyroidism. These children
had no systemic signs of hyperthyroidism. Treatment with neomercazole resulted in good control
of their hyperkinetic behavior and subsequent improvement in language function attributable to an
increased attention span, thereby facilitating speech therapy. . . ."
Thyroid function in attention deficit and hyperactivity disorder.
Toren P et al.,
J Psychiatr Res 1997 May-Jun;31(3):359-63
. . . we performed a replication study to clarify the
issue and establish clinical guidelines. Thyroid tests were performed in 43 ADHD children and 28
age- and gender-matched controls. Sixteen ADHD children showed total triiodothyronine (TT3)
levels which were slightly above the upper limit of normal, but no significant difference in TT3
values was noted between the ADHD and the control groups. Moreover, none of the ADHD
subjects had abnormal levels of total thyroxine, free thyroxine, thyroid stimulating hormone or
total triiodothyronine reuptake. The present study supplies additional evidence for the lack of an
association between thyroid function and ADHD, and counters the suggestion that thyroid
function be routinely screened for in ADHD children."
NOTE: Consider whether you agree with the author's conclusion. More than 37% of the children were slightly above the upper limit of normal. If, in 43 children, a relatively rare serious thyroid problem is not found, is that really grounds not even to look for such a problem? If the problem cannot be fixed, perhaps it does not pay to know about it. However, since thyroid dysfunction can be treated, what is the sense of not checking to rule it out? No one is suggesting that thyroid dysfunction is the only cause of ADHD.
Thyroid function in a population of children with attention deficit
Valentine J, Rossi E, O'Leary P, Parry TS, Kurinczuk JJ, Sly P,
J Paediatr Child Health 1997 Apr;33(2):117-20
. . .The prevalence of thyroid hormone abnormalities in the study population
was 2.3% . . . There were no cases of generalized resistance to thyroid
hormone. The prevalence of thyroid hormone abnormalities in the general population of children
and adolescents has been reported to vary between 1 and 3.7%. CONCLUSION: Routine
thyroid hormone screening is not indicated in children with non-familial ADHD."
NOTE: In the opinion of a parent who is not a medical professional -- Considering the expense and heartbreak of treating a child with ADHD for many years when there is even a 2% chance of finding a correctable problem, it seems illogical not to screen for it. A thyroid test is neither invasive nor dangerous.
Attention-deficit hyperactivity disorder and thyroid function.
Weiss RE, Stein MA, Trommer B, Refetoff S,
J Pediatr 1993 Oct;123(4):539-45
. . . We report a prospective screening study for thyroid
abnormalities in 277 children with ADHD by measurement of serum levels of total thyroxine, free
thyroxine index, and thyrotropin. Fourteen children with ADHD had thyroid function test
abnormalities: six had a normal free thyroxine index and elevated thyroxine level (group 1); three
had a high free thyroxine index and a normal thyrotropin level (group 2); and five had a low free
thyroxine index with a normal thyrotropin level (group 3). . . . Although the
prevalence of ADHD in subjects with GRTH [general resistance to thyroid hormone] has been reported to be 46%, the overall
prevalence of GRTH must be less than 1:2500 because we failed to detect GRTH in the 277
children with ADHD studied. We conclude that the prevalence of thyroid abnormalities is higher
(5.4%) in children with ADHD than in the normal population (< 1%)."
Phenotype differences of resistance to thyroid hormone in two
unrelated families with an identical mutation in the thyroid hormone
receptor beta gene (R320C). Weiss RE, Tunca H, Knapple WL, Faas FH, Refetoff S,
Thyroid 1997 Feb;7(1):35-8
"... In one of the two families higher
concentrations of free T4 were required to maintain a normal TSH level in affected subjects......it is uncertain whether the higher thyroid hormone levels
prevented the occurrence of hyperactivity and attention deficit."
Behavioral effects of liothyronine (L-T3) in children with attention deficit
hyperactivity disorder in the presence and absence of resistance to thyroid hormone.
Weiss RE, Stein MA, Refetoff S,
Thyroid 1997 Jun;7(3):389-93
Evidence that the thyroid may play a role in the pathogenesis of attention deficit hyperactivity
disorder (ADHD) comes from observations that 48% to 73% of children with the syndrome of
resistance to thyroid hormone (RTH) have ADHD. . . . A prospective, randomized, double-blinded, placebo-controlled,
cross-over study was conducted
. . . In children with RTH and ADHD, particularly those that exhibit hyperactivity,
L-T3 in supraphysiological doses may be beneficial in reducing hyperactivity and impulsivity. In
the majority of children with ADHD who do not have RTH, L-T3 treatment has no effect or may
Differences in thyroid function studies in acutely manic adolescents with
and without attention deficit hyperactivity disorder (ADHD).
West SA, Sax KW, Stanton SP, Keck PE Jr, McElroy SL, Strakowski SM,
Psychopharmacol Bull 1996;32(1):63-6
The purpose of this study was to compare basal thyroid indices in adolescent (ages 12 to 18)
bipolar patients with and without attention deficit hyperactivity disorder (ADHD). . . . Twenty patients (66%) had comorbid ADHD. The
mean serum T4 concentration in this group was significantly lower than it was for patients with
bipolar disorder alone. There were no significant differences between groups in serum T3 or TSH
concentrations. . . this may
have important implications regarding the potential benefits of thyroid supplementation in
adolescents with bipolar disorder and comorbid ADHD who do not respond to mood stabilizers